scholarly journals The dark side of SARS-CoV-2 rapid antigen testing: screening asymptomatic patients

2021 ◽  
Author(s):  
Giorgia Caruana ◽  
Laure-Line Lebrun ◽  
Oriane Aebischer ◽  
Onya Opota ◽  
Luis Urbano ◽  
...  
Keyword(s):  
Hospital Admissions ◽  
Screening Method ◽  
Dark Side ◽  
Pcr Analysis ◽  
Rt Pcr ◽  
Asymptomatic Patients ◽  
Antigen Tests ◽  
Outpatient Settings ◽  
Antigen Testing

AbstractMost of the reports describing SARS-CoV-2 rapid antigen tests (RATs) performances derive from COVID-19 symptomatic subjects in outpatient settings during periods of highest incidence of infections and high rates of hospital admissions. Here we investigated the role of RATs in an Emergency Department, as a screening tool before admission for COVID-19 asymptomatic patients. Each patient was screened with two simultaneous nasopharyngeal swabs: one immediately analyzed at the bedside using RAT and the other sent to the laboratory for RT-PCR analysis. A total of 116 patients were screened at hospital admission in a 250-bed community hospital in Morges (EHC), Switzerland. With a disease prevalence of 6% based on RT-PCR results, RAT detected only two out of seven RT-PCR positive patients (sensitivity 28.6%) and delivered two false positive results (specificity 98.2%), thus resulting not fiable enough to be used as a screening method in this clinical scenario.

scholarly journals Five Antigen Tests for SARS-CoV-2: Virus Viability Matters

Viruses ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 684
Author(s):  
Miroslav Homza ◽  
Hana Zelena ◽  
Jaroslav Janosek ◽  
Hana Tomaskova ◽  
Eduard Jezo ◽  
...  
Keyword(s):  
False Negative ◽  
Antigen Test ◽  
Rt Pcr ◽  
False Negatives ◽  
Predictive Values ◽  
Asymptomatic Patients ◽  
High Prevalence ◽  
Antigen Tests ◽  
Antigen Testing ◽  
Excellent Tool

Antigen testing for SARS-CoV-2 (AGT) is generally considered inferior to RT-PCR testing in terms of sensitivity. However, little is known about the infectiousness of RT-PCR positive patients who pass undetected by AGT. In a screening setting for mildly symptomatic or asymptomatic patients with high COVID-19 prevalence (30–40%), 1141 patients were tested using one of five AGTs and RT-PCR. Where the results differed, virus viability in the samples was tested on cell culture (CV-1 cells). The test battery included AGTs by JOYSBIO, Assure Tech, SD Biosensor, VivaChek Biotech and NDFOS. Sensitivities of the ATGs compared to RT-PCR ranged from 42% to 76%. The best test yielded a 76% sensitivity, 97% specificity, 92% positive, and 89% negative predictive values, respectively. However, in the best performing ATG tests, almost 90% of samples with “false negative” AGT results contained no viable virus. Corrected on the virus viability, sensitivities grew to 81%–97% and, with one exception, the tests yielded high specificities >96%. Performance characteristics of the best test after adjustment were 96% sensitivity, 97% specificity, 92% positive, and 99% negative predictive values (high prevalence population). We, therefore, believe that virus viability should be considered when assessing the AGT performance. Also, our results indicate that a well-performing antigen test could in a high-prevalence setting serve as an excellent tool for identifying patients shedding viable virus. We also propose that the high proportion of RT-PCR-positive samples containing no viable virus in the group of “false negatives” of the antigen test should be further investigated with the aim of possibly preventing needless isolation of such patients.

scholarly journals Implementing SARS-CoV-2 Rapid Antigen Testing in the Emergency Ward of a Swiss University Hospital: The INCREASE Study

2021 ◽  
Vol 9 (4) ◽  
pp. 798
Author(s):  
Giorgia Caruana ◽  
Antony Croxatto ◽  
Eleftheria Kampouri ◽  
Antonios Kritikos ◽  
Onya Opota ◽  
...  
Keyword(s):  
Immunoglobulin A ◽  
University Hospital ◽  
Lower Sensitivity ◽  
Clinical Settings ◽  
Rt Pcr ◽  
Emergency Ward ◽  
Viral Loads ◽  
Asymptomatic Patients ◽  
Asymptomatic Subjects ◽  
Antigen Testing

Following the Swiss Federal Office of Public Health (FOPH) authorization of the rapid antigen test (RAT), we implemented the use of the RAT in the emergency ward of our university hospital for patients’ cohorting. RAT triaging in association with RT-PCR allowed us to promptly isolate positive patients and save resources. Among 532 patients, overall sensitivities were 48.3% for Exdia and 41.2% for Standard Q®, PanbioTM and BD Veritor™. All RATs exhibited specificity above 99%. Sensitivity increased to 74.6%, 66.2%, 66.2% and 64.8% for Exdia, Standard Q®, PanbioTM and BD Veritor™, respectively, for viral loads above 105 copies/mL, to 100%, 97.8%, 96.6% and 95.6% for viral loads above 106 copies/mL and 100% for viral loads above 107 copies/mL. Sensitivity was significantly higher for patients with symptoms onset within four days (74.3%, 69.2%, 69.2% and 64%, respectively) versus patients with the evolution of symptoms longer than four days (36.8%, 21.1%, 21.1% and 23.7%, respectively). Among COVID-19 asymptomatic patients, sensitivity was 33%. All Immunoglobulin-A-positive patients resulted negative for RAT. The RAT might represent a useful resource in selected clinical settings as a complementary tool in RT-PCR for rapid patient triaging, but the lower sensitivity, especially in late presenters and COVID-19 asymptomatic subjects, must be taken into account.

Islet Co-Expression of CD133 and ABCB5 in Human Retinoblastoma Specimens

2021 ◽  
Author(s):  
Marco Zschoche ◽  
Sergej Skosyrski ◽  
Neele Babst ◽  
Mahdy Ranjbar ◽  
Felix Rommel ◽  
...  
Keyword(s):  
Treatment Resistance ◽  
Sphingosine Kinase ◽  
Immunohistochemical Analysis ◽  
Pcr Analysis ◽  
Sphingosine Kinase 1 ◽  
Rt Pcr ◽  
Beam Radiation ◽  
Sphingosine Kinase 2 ◽  
Human Retinoblastoma

Abstract Background The role of CD133 und ABCB5 is discussed in treatment resistance in several types of cancer. The objective of this study was to evaluate whether CD133+/ABCB5+ colocalization differs in untreated, in beam radiation treated, and in chemotherapy treated retinoblastoma specimens. Additionally, CD133, ABCB5, sphingosine kinase 1, and sphingosine kinase 2 gene expression was analyzed in WERI-RB1 (WERI RB1) and etoposide-resistant WERI RB1 subclones (WERI ETOR). Methods Active human untreated retinoblastoma specimens (n = 12), active human retinoblastoma specimens pretreated with beam radiation before enucleation (n = 8), and active human retinoblastoma specimens pretreated with chemotherapy before enucleation (n = 7) were investigated for localization and expression of CD133 and ABCB5 by immunohistochemistry. Only specimens with IIRC D, but not E, were included in this study. Furthermore, WERI RB1 and WERI ETOR cell lines were analyzed for CD133, ABCB5, sphingosine kinase 1, and sphingosine kinase 2 by the real-time polymerase chain reaction (RT-PCR). Results Immunohistochemical analysis revealed the same amount of CD133+/ABCB5+ colocalization islets in untreated and treated human retinoblastoma specimens. Quantitative RT-PCR analysis showed a statistically significant upregulation of CD133 in WERI ETOR (p = 0.002). No ABCB5 expression was detected in WERI RB1 and WERI ETOR. On the other hand, SPHK1 (p = 0.0027) and SPHK2 (p = 0.017) showed significant downregulation in WERI ETOR compared to WERI RB1. Conclusions CD133+/ABCB5+ co-localization islets were noted in untreated and treated human retinoblastoma specimens. Therefore, we assume that CD133+/ABCB5+ islets might play a role in retinoblastoma genesis, but not in retinoblastoma treatment resistance.

The Critical Role of Peptidyl-Prolyl cis/trans Isomerase, Pin1 in Acute Myeloid Leukemia with C/EBPalpha Mutations.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2213-2213
Author(s):  
J. Pulikkan ◽  
A. Peer Zada ◽  
M. Geletu ◽  
V. Dengler ◽  
Daniel G. Tenen ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Dominant Negative ◽  
Pcr Analysis ◽  
Wild Type ◽  
Rt Pcr ◽  
Promoter Assay ◽  
Type C ◽  
Acute Myeloid

Abstract CCAAT enhancer binding protein alpha (C/EBPα) is a myeloid specific transcription factor that coordinates cellular differentiation and cell cycle arrest. Loss of C/EBPα expression or function in leukemic blasts contributes to a block in myeloid cell differentiation. C/EBPα is mutated in around 9% of acute myeloid leukemia (AML). The mutations reported in C/EBPα are frame shift mutations and point mutations at basic region Leucine zipper. The mutant form of C/EBPα ie C/EBPα-p30 exhibits dominant negative function over the wild type protein. The role of peptidyl-prolyl cis/trans isomerase, Pin1 in tumorogenesis and its overexpression in many cancers led us to investigate its role in acute myeloid leukemia with C/EBPα mutation. Here we show that Pin1 is upregulated in patients with acute myeloid leukemia by affymetrix analysis. By quantitative Real-Time RT-PCR analysis, we show C/EBPα-p30 could induce Pin1 transcription, while the wild type C/EBPα downregulates Pin1 expression. Luciferase promoter assay for the Pin1 promoter shows that wild type C/EBPα is able to block Pin1 promoter activity. Mean while, C/EBPα-p30 couldn’t block Pin1 promotor activity. By silencing Pin1 by RNA Interference as well as with inhibitor against Pin1 (PiB) we could show myeloid differentiation in human CD34+ cord blood cells as well as in Kasumi-6 cells as assessed by FACS analysis with granulocytic markers. We investigated the mechanism underlying the dominant negative action of C/EBPα-p30 over the wild type protein. We report that Pin1 increases the transcriptional activity of the oncogene c-jun. We also show that c-jun blocks the DNA binding and transactivation of C/EBPα protein as assessed by gel shift assay and promoter assay respectively. We have previously shown that c-jun expression is high in AML patients with C/EBPα mutation and c-jun could block C/EBPα function by protein-protein interaction. Quantitative Real-Time RT-PCR analysis shows that inhibition of Pin1 by the inhibitor PiB downregulates c-jun mRNA expression. In conclusion, inhibition of Pin1 leads to granulocytic differentiation. Our results show Pin1 as a novel target in treating AML patients with C/EBPα mutation.

scholarly journals Role of Rapid Antigen Testing in Population-Based SARS-CoV-2 Screening

2021 ◽  
Vol 10 (17) ◽  
pp. 3854
Author(s):  
Vicente Martín-Sánchez ◽  
Tania Fernández-Villa ◽  
Ana Carvajal Urueña ◽  
Ana Rivero Rodríguez ◽  
Sofía Reguero Celada ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Diagnostic Test ◽  
Internal Validity ◽  
High Specificity ◽  
Population Based ◽  
Predictive Values ◽  
Asymptomatic Patients ◽  
Screening Performance ◽  
Antigen Testing

This study evaluates a population-based screening of asymptomatic people, using a rapid antigen diagnostic test (RADT), in areas of high transmission. To detect sources of SARS-CoV-2 infection, nasopharyngeal samples were taken and were tested using RADT. Confirmatory RT-qPCR tests were performed in both positive and negative cases. The internal validity of the RADT, the prevalence of infection, and the positive and negative predictive values (PPV and NPV) were estimated, based on the percentages of confirmed cases with 95% confidence interval. Of the 157,920 people registered, 50,492 participated in the screening; 50,052 were negative, and 440 were positive on the RADT (0.87%). A total of 221 positive RADT samples were reanalysed using RT-qPCR and 214 were confirmed as positive (96.8%; 95% CI: 93.5–98.7%), while 657 out of 660 negative RADT samples were confirmed as RT-qPCR negative (99.5%; 95% CI 98.7–99.9%). The sensitivity obtained was 65.1% (38.4–90.2%) and the specificity was 99.97% (99.94–99.99%). The prevalence of infection was 1.30% (0.95–2.13%). The PPVs were 95.4% (85.9–98.9%) and 97.9% (93.3–99.5%), respectively, while the NPVs were 99.7% (99.4–100%) and 99.2% (98.7–100%), respectively. The high specificity found allow us to report a high screening performance in asymptomatic patients, even in areas where the prevalence of infection was less than 2%.

scholarly journals Sensitivity of rapid antigen testing and RT-PCR performed on nasopharyngeal swabs versus saliva samples in COVID-19 hospitalized patients: results of a prospective comparative trial (RESTART)

2021 ◽  
Author(s):  
Antonios Kritikos ◽  
Giorgia Caruana ◽  
René Brouillet ◽  
John-Paul Miroz ◽  
Abed-Maillard Samia ◽  
...  
Keyword(s):  
Comparative Trial ◽  
Hospitalized Patients ◽  
Rt Pcr ◽  
Duration Of Symptoms ◽  
Non Invasive ◽  
Viral Transport Medium ◽  
One Step ◽  
Antigen Tests ◽  
Low Sensitivity ◽  
Antigen Testing

AbstractObjectivesSaliva sampling could serve as an alternative non-invasive sample for SARS-CoV-2 diagnosis while rapid antigen testing (RAT) might help to mitigate the shortage of reagents sporadically encountered with RT-PCR. Thus, in the RESTART study we compared antigen and RT-PCR testing methods on nasopharyngeal (NP) swabs and salivary samples.MethodsWe conducted a prospective observational study among COVID-19 hospitalized patients between 10th December 2020 and 1st February 2021. Paired saliva and NP samples were investigated by RT-PCR (Cobas 6800, Roche-Switzerland) and by two rapid antigen tests: One Step Immunoassay Exdia® COVID-19 Ag (Precision Biosensor, Korea) and Standard Q® COVID-19 Rapid Antigen Test (Roche-Switzerland).ResultsA total of 58 paired NP-saliva specimens were collected. Thirty-two of 58 (55%) patients were hospitalized in the intensive care unit and the median duration of symptoms was 11 days (IQR 5-19). NP and salivary RT-PCR exhibited sensitivity of 98% and 69% respectively whereas the specificity of these RT-PCRs assays were of 100%. NP RAT exhibited much lower diagnostic performances with sensitivities of 35% and 41% for the Standard Q® and Exdia® assays respectively, when a wet-swab approach was used (i.e. when the swab was diluted in the viral transport medium (VTM) before testing). The sensitivity of the dry-swab approach was slightly better (47%). These antigen tests exhibited very low sensitivity (4 and 8%) when applied to salivary swabs.ConclusionsNasopharyngeal RT-PCR is the most accurate test for COVID-19 diagnosis in hospitalized patients. RT-PCR on salivary samples may be used when nasopharyngeal swabs are contraindicated. RAT are not appropriate for hospitalized patients.

scholarly journals Complex N-Glycans Are Important for Normal Fruit Ripening and Seed Development in Tomato

2021 ◽  
Vol 12 ◽  
Author(s):  
Heidi Kaulfürst-Soboll ◽  
Melanie Mertens-Beer ◽  
Randolf Brehler ◽  
Markus Albert ◽  
Antje von Schaewen
Keyword(s):  
Rna Interference ◽  
Fruit Ripening ◽  
Reproductive Stage ◽  
Pcr Analysis ◽  
Plant Responses ◽  
Rt Pcr ◽  
Signaling Crosstalk ◽  
Long Time ◽  
Glycan Modification

Complex N-glycan modification of secretory glycoproteins in plants is still not well understood. Essential in animals, where a lack of complex N-glycans is embryo-lethal, their presence in plants seemed less relevant for a long time mostly because Arabidopsis thaliana cgl1 mutants lacking N-acetyl-glucosaminyltransferase I (GNTI, the enzyme initiating complex N-glycan maturation in the Golgi apparatus) are viable and showed only minor impairments regarding stress tolerance or development. A different picture emerged when a rice (Oryza sativa) gntI T-DNA mutant was found to be unable to reach the reproductive stage. Here, we report on tomato (Solanum lycopersicum) lines that showed severe impairments upon two RNA interference (RNAi) approaches. Originally created to shed light on the role of core α1,3-fucose and β1,2-xylose residues in food allergy, plants with strongly reduced GNTI activity developed necrotic fruit-attached stalks and early fruit drop combined with patchy incomplete ripening. Correspondingly, semiquantitative RT-PCR of the abscission zone (az) revealed an increase of abscission markers. Also, GNTI-RNA interference (RNAi) plants were more susceptible to sporadic infection. To obtain vital tomatoes with comparable low allergenic potential, Golgi α-mannosidase II (MANII) was chosen as the second target. The resulting phenotypes were oppositional: MANII-reduced plants carried normal-looking fruits that remained attached for extended time without signs of necrosis. Fruits contained no or only few, but enlarged, seeds. Furthermore, leaves developed rolled-up rims simultaneously during the reproductive stage. Trials to cross MANII-reduced plants failed, while GNTI-reduced plants could be (back-)crossed, retaining their characteristic phenotype. This phenotype could not be overcome by ethephon or indole-3-acetic acid (IAA) application, but the latter was able to mimic patchy fruit ripening in wild-type. Phytohormones measured in leaves and 1-aminocyclopropane-1-carboxylic acid (ACC) contents in fruits showed no significant differences. Together, the findings hint at altered liberation/perception of protein-bound N-glycans, known to trigger auxin-like effects. Concomitantly, semiquantitative RT-PCR analysis revealed differences in auxin-responsive genes, indicating the importance of complex N-glycan modification for hormone signaling/crosstalk. Another possible role of altered glycoprotein life span seems subordinate, as concluded from transient expression of Arabidopsis KORRIGAN KOR1-GFP fusion proteins in RNAi plants of Nicotiana benthamiana. In summary, our analyses stress the importance of complex N-glycan maturation for normal plant responses, especially in fruit-bearing crops like tomato.

scholarly journals Diagnostic performance of a novel digital immunoassay (RapidTesta SARS-CoV-2): a prospective observational study with 1,127 nasopharyngeal samples

2021 ◽  
Author(s):  
Hiromichi Suzuki ◽  
Yusaku Akashi ◽  
Atsuo Ueda ◽  
Yoshihiko Kiyasu ◽  
Yuto Takeuchi ◽  
...  
Keyword(s):  
Diagnostic Performance ◽  
Prospective Observational Study ◽  
Test Results ◽  
Antigen Test ◽  
Rt Pcr ◽  
Asymptomatic Patients ◽  
Pcr Method ◽  
Antigen Tests ◽  
Positive Line ◽  
Test Cassette

Introduction: Digital immunoassays are generally regarded as superior tests for the detection of infectious disease pathogens, but there have been insufficient data concerning SARS-CoV-2 immunoassays. Methods: We prospectively evaluated a novel digital immunoassay (RapidTesta SARS-CoV-2). Two nasopharyngeal samples were simultaneously collected for antigen tests and RT-PCR. Real-time RT-PCR for SARS-CoV-2, using a method developed by the National Institute of Infectious Diseases, Japan, served as the reference RT-PCR method. Results: During the study period, 1,127 nasopharyngeal samples (symptomatic patients: 802, asymptomatic patients: 325) were evaluated. For digital immunoassay antigen tests, the sensitivity was 78.3% (95% CI: 67.3%-87.1%) and the specificity was 97.6% (95% CI: 96.5%-98.5%). When technicians visually analyzed the antigen test results, the sensitivity was 71.6% (95% CI: 59.9%-81.5%) and the specificity was 99.2% (95% CI: 98.5%-99.7%). Among symptomatic patients, the sensitivity was 89.4% (95% CI; 76.9%-96.5%) with digital immunoassay antigen tests, and 85.1% (95% CI; 71.7%-93.8%) with visually analyzed the antigen test, respectively. Conclusions: The findings indicated that RapidTesta SARS-CoV-2 analysis with the DIA device had sufficient analytical performance for the detection of SARS-CoV-2 in nasopharyngeal samples. When positive DIA results are recorded without a visually recognizable red line at the positive line location on the test cassette, additional RT-PCR evaluation should be performed.

scholarly journals On Pilot Massive COVID-19 Testing by Antigen Tests in Europe. Case Study: Slovakia

2021 ◽  
Vol 13 (1) ◽  
pp. 45-57
Author(s):  
Jaroslav Frnda ◽  
Marek Durica
Keyword(s):  
Mathematical Models ◽  
National Health ◽  
Health Authority ◽  
False Positive ◽  
Infection Rates ◽  
Rt Pcr ◽  
Sick People ◽  
Antigen Tests ◽  
Antigen Testing

This paper provides a summary of mass COVID-19 testing of almost the entire population in Slovakia by antigen tests. We focused on the results delivered by two testing rounds and analyzed the benefits and weaknesses of such type of testing. We prepared mathematical models to critically examine the effectiveness of the testing, and we also estimated the number of potentially sick people that would become infected by those marked as positives by antigen tests. Our calculations have proven that antigen testing in hotspots can flatten the curve of daily newly reported cases significantly, but in regions with low-risk of COVID-19, the benefit of such testing is questionable. As for the regions with low infection rates, we could only estimate the proportion of true and false-positive cases because the national health authority had not validated the results by RT–PCR tests. Therefore, this work can serve as an introductory study on the first nationwide testing by antigen tests in Europe.

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